3p87
From Proteopedia
(Difference between revisions)
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| - | + | ==Structure of human PCNA bound to RNASEH2B PIP box peptide== | |
| - | + | <StructureSection load='3p87' size='340' side='right' caption='[[3p87]], [[Resolution|resolution]] 2.99Å' scene=''> | |
| - | + | == Structural highlights == | |
| - | + | <table><tr><td colspan='2'>[[3p87]] is a 12 chain structure with sequence from [http://en.wikipedia.org/wiki/Human Human]. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=3P87 OCA]. For a <b>guided tour on the structure components</b> use [http://oca.weizmann.ac.il/oca-docs/fgij/fg.htm?mol=3P87 FirstGlance]. <br> | |
| - | ==Disease== | + | </td></tr><tr id='related'><td class="sblockLbl"><b>[[Related_structure|Related:]]</b></td><td class="sblockDat">[[3p83|3p83]], [[1axc|1axc]]</td></tr> |
| + | <tr id='gene'><td class="sblockLbl"><b>[[Gene|Gene:]]</b></td><td class="sblockDat">PCNA ([http://www.ncbi.nlm.nih.gov/Taxonomy/Browser/wwwtax.cgi?mode=Info&srchmode=5&id=9606 HUMAN])</td></tr> | ||
| + | <tr id='resources'><td class="sblockLbl"><b>Resources:</b></td><td class="sblockDat"><span class='plainlinks'>[http://oca.weizmann.ac.il/oca-docs/fgij/fg.htm?mol=3p87 FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=3p87 OCA], [http://www.rcsb.org/pdb/explore.do?structureId=3p87 RCSB], [http://www.ebi.ac.uk/pdbsum/3p87 PDBsum]</span></td></tr> | ||
| + | </table> | ||
| + | == Disease == | ||
[[http://www.uniprot.org/uniprot/RNH2B_HUMAN RNH2B_HUMAN]] Aicardi-Goutieres syndrome. The disease is caused by mutations affecting the gene represented in this entry. | [[http://www.uniprot.org/uniprot/RNH2B_HUMAN RNH2B_HUMAN]] Aicardi-Goutieres syndrome. The disease is caused by mutations affecting the gene represented in this entry. | ||
| - | + | == Function == | |
| - | ==Function== | + | |
[[http://www.uniprot.org/uniprot/PCNA_HUMAN PCNA_HUMAN]] Auxiliary protein of DNA polymerase delta and is involved in the control of eukaryotic DNA replication by increasing the polymerase's processibility during elongation of the leading strand. Induces a robust stimulatory effect on the 3'-5' exonuclease and 3'-phosphodiesterase, but not apurinic-apyrimidinic (AP) endonuclease, APEX2 activities. Has to be loaded onto DNA in order to be able to stimulate APEX2. Plays a key role in DNA damage response (DDR) by being conveniently positioned at the replication fork to coordinate DNA replication with DNA repair and DNA damage tolerance pathways. Acts as a loading platform to recruit DDR proteins that allow completion of DNA replication after DNA damage and promote postreplication repair: Monoubiquitinated PCNA leads to recruitment of translesion (TLS) polymerases, while 'Lys-63'-linked polyubiquitination of PCNA is involved in error-free pathway and employs recombination mechanisms to synthesize across the lesion.<ref>PMID:19443450</ref> <ref>PMID:18719106</ref> [[http://www.uniprot.org/uniprot/RNH2B_HUMAN RNH2B_HUMAN]] Non catalytic subunit of RNase H2, an endonuclease that specifically degrades the RNA of RNA:DNA hybrids. Participates in DNA replication, possibly by mediating the removal of lagging-strand Okazaki fragment RNA primers during DNA replication. Mediates the excision of single ribonucleotides from DNA:RNA duplexes.<ref>PMID:21177858</ref> <ref>PMID:16845400</ref> | [[http://www.uniprot.org/uniprot/PCNA_HUMAN PCNA_HUMAN]] Auxiliary protein of DNA polymerase delta and is involved in the control of eukaryotic DNA replication by increasing the polymerase's processibility during elongation of the leading strand. Induces a robust stimulatory effect on the 3'-5' exonuclease and 3'-phosphodiesterase, but not apurinic-apyrimidinic (AP) endonuclease, APEX2 activities. Has to be loaded onto DNA in order to be able to stimulate APEX2. Plays a key role in DNA damage response (DDR) by being conveniently positioned at the replication fork to coordinate DNA replication with DNA repair and DNA damage tolerance pathways. Acts as a loading platform to recruit DDR proteins that allow completion of DNA replication after DNA damage and promote postreplication repair: Monoubiquitinated PCNA leads to recruitment of translesion (TLS) polymerases, while 'Lys-63'-linked polyubiquitination of PCNA is involved in error-free pathway and employs recombination mechanisms to synthesize across the lesion.<ref>PMID:19443450</ref> <ref>PMID:18719106</ref> [[http://www.uniprot.org/uniprot/RNH2B_HUMAN RNH2B_HUMAN]] Non catalytic subunit of RNase H2, an endonuclease that specifically degrades the RNA of RNA:DNA hybrids. Participates in DNA replication, possibly by mediating the removal of lagging-strand Okazaki fragment RNA primers during DNA replication. Mediates the excision of single ribonucleotides from DNA:RNA duplexes.<ref>PMID:21177858</ref> <ref>PMID:16845400</ref> | ||
| + | <div style="background-color:#fffaf0;"> | ||
| + | == Publication Abstract from PubMed == | ||
| + | Ribonuclease H2 is the major nuclear enzyme degrading cellular RNA/DNA hybrids in eukaryotes and the sole nuclease known to be able to hydrolyze ribonucleotides misincorporated during genomic replication. Mutation in RNASEH2 causes Aicardi-Goutieres syndrome, an auto-inflammatory disorder that may arise from nucleic acid byproducts generated during DNA replication. Here, we report the crystal structures of Archaeoglobus fulgidus RNase HII in complex with PCNA, and human PCNA bound to a C-terminal peptide of RNASEH2B. In the archaeal structure, three binding modes are observed as the enzyme rotates about a flexible hinge while anchored to PCNA by its PIP-box motif. PCNA binding promotes RNase HII activity in a hinge-dependent manner. It enhances both cleavage of ribonucleotides misincorporated in DNA duplexes, and the comprehensive hydrolysis of RNA primers formed during Okazaki fragment maturation. In addition, PCNA imposes strand specificity on enzyme function, and by localizing RNase H2 and not RNase H1 to nuclear replication foci in vivo it ensures that RNase H2 is the dominant RNase H activity during nuclear replication. Our findings provide insights into how type 2 RNase H activity is directed during genome replication and repair, and suggest a mechanism by which RNase H2 may suppress generation of immunostimulatory nucleic acids. | ||
| - | + | PCNA directs type 2 RNase H activity on DNA replication and repair substrates.,Bubeck D, Reijns MA, Graham SC, Astell KR, Jones EY, Jackson AP Nucleic Acids Res. 2011 Jan 17. PMID:21245041<ref>PMID:21245041</ref> | |
| - | + | ||
| + | From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.<br> | ||
| + | </div> | ||
==See Also== | ==See Also== | ||
*[[Proliferating Cell Nuclear Antigen|Proliferating Cell Nuclear Antigen]] | *[[Proliferating Cell Nuclear Antigen|Proliferating Cell Nuclear Antigen]] | ||
| - | + | == References == | |
| - | == | + | <references/> |
| - | + | __TOC__ | |
| + | </StructureSection> | ||
[[Category: Human]] | [[Category: Human]] | ||
| - | [[Category: Astell, K R | + | [[Category: Astell, K R]] |
| - | [[Category: Bubeck, D | + | [[Category: Bubeck, D]] |
| - | [[Category: Graham, S C | + | [[Category: Graham, S C]] |
| - | [[Category: Jackson, A P | + | [[Category: Jackson, A P]] |
| - | [[Category: Jones, E Y | + | [[Category: Jones, E Y]] |
| - | [[Category: Reijns, M A | + | [[Category: Reijns, M A]] |
[[Category: Dna binding]] | [[Category: Dna binding]] | ||
[[Category: Dna clamp]] | [[Category: Dna clamp]] | ||
Revision as of 22:56, 3 January 2015
Structure of human PCNA bound to RNASEH2B PIP box peptide
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Categories: Human | Astell, K R | Bubeck, D | Graham, S C | Jackson, A P | Jones, E Y | Reijns, M A | Dna binding | Dna clamp | Dna repair | Dna replication | Fen-1 | Helicase | Hydrolase-dna binding protein complex | Ligase | Nuclease | Nucleus | Pip-box motif | Polymerase | Processivity factor | Rnase h2 | Sliding clamp
